A multi-institutional survey of the quality of life after treatment for uterine cervical cancer: a comparison between radical radiotherapy and surgery in Japan

This study aimed to research the post-treatment quality of life (QOL) between radiotherapy (RT)- and operation (OP)-treated early cervical cancer survivors, using separate questionnaires for physicians and patients. We administered an observational questionnaire to patients aged 20–70 years old with Stages IB1–IIB cervical cancer who had undergone RT or OP and without recurrence as outpatients for ≥6 months after treatment. We divided 100 registered patients equally into two treatment groups (n = 50 each). The average age was 53 and 44 years in the RT and OP groups, respectively. The RT group included 34 and 66% Stage I and II patients, respectively, whereas the OP group included 66 and 34% Stage I and II patients, respectively. The OP group included 58% of patients with postoperative RT. Combination chemotherapy was performed in 84 and 48% of patients in the RT and OP groups, respectively. On the physicians’ questionnaire, we observed significant differences in bone marrow suppression (RT) and leg edema (OP). On the patients’ questionnaire, significantly more patients had dysuria and leg edema in the OP group than in the RT group, and severe (Score 4–5) leg edema was significantly higher in the post-operative RT group than in the OP only group. The frequency of sexual intercourse decreased after treatment in both groups. On the patients’ questionnaire, there were no significant differences between the two groups regarding sexual activity. These findings are useful to patients and physicians for shared decision-making in treatment choices. The guidance of everyday life and health information including sexual life after treatment is important.     

Footwear exchange has no influence on the incidence of febrile neutropenia in patients undergoing chemotherapy for hematologic malignancies.

OBJECTIVE: To determine whether footwear exchange affects the incidence of febrile neutropenia among patients undergoing chemotherapy for hematologic malignancies. DESIGN: Open trial with historical comparison. SETTING: The 12-bed high-efficiency particulate air-filtered hematology unit at Osaka University Hospital, Suita, Japan. PATIENTS: Those with hematologic malignancies who underwent chemotherapy from January 1997 through January 2003. Footwear exchange was discontinued in January 2000. METHODS: The surveillance system was based on the National Nosocomial Infections Surveillance System of the Centers for Disease Control and Prevention. Rates of febrile neutropenia were calculated for neutropenic patient-days (ie, days with neutropenia < 500/microL). RESULTS: From January 1997 through December 1999 and from February 2000 through January 2003, 58 and 54 patients endured 237 and 184 neutropenic periods following chemotherapy, and their total neutropenic days were 3,123 and 2,503, respectively. They showed episodes of febrile neutropenia 89 and 68 times, respectively. Infection rates were 28.5 and 27.2 per 1,000 neutropenic patient-days (P = .83), respectively. CONCLUSION: The incidence of febrile neutropenia was not affected by footwear exchange. In hematology units, changing shoes does not appear to affect the rate of infections during neutropenic periods.     

Growth hormone-releasing hormone and gonadotropin-releasing hormone stimulate nitric oxide production in 17beta-estradiol-primed rat anterior pituitary cells

It was reported that neuronal nitric oxide synthase (nNOS) was expressed only in gonadotrophs and folliculo-stellate cells in the anterior lobe of the pituitary gland. However, recent studies have demonstrated the occurrence of nNOS in the somatotrophs and lactotrophs. In the present study, we investigated effects of growth hormone-releasing hormone (GHRH), gonadotropin-releasing hormone (GnRH), and 17β-estradiol on nitric oxide (NO) release in cultured rat anterior pituitary cells in vitro. The NO ₂ ⁻ level in the incubation medium of the rat anterior pituitary cells was dependent on the cell density. Pretreatment with 10 μM 17β-estradiol resulted in an increase in medium NO ₂ ⁻ level. GHRH and GnRH failed to change medium NO ₂ ⁻ levels, but they elicited increases in medium NO ₂ ⁻ levels in estrogen-treated cells. The GHRH-induced increase in NO ₂ ⁻ level was inhibited by Nχ-nitro-l-arginine methyl ester, a NOS inhibitor. These findings suggest that GnRH and GHRH could activate nNOS in the gonadotrophs and the somatotrophs, respectively.     

Common antigenicities between Angiostrongylus cantonensis and various species of snails

Studies on common antigenicities were carried out by using rabbit sera immunized with Angiostrongylus cantonensis adult worms or the third stage larvae and antigens of various species of snails and vice versa by the immunoblotting technique. The results obtained are summarized as follows: (1) Common antigenicities between A. cantonensis adult worms and snails susceptible to A. cantonensis were observed in a range of molecular weights of 14.3 to 200 kDa. In Puerto Rican pigmented Biomphalaria glabrata and Achatina fulca, which had high infection rates with A. cantonensis, we recognized 15 to 16 bands against the adult worm, especially the band with a molecular weight of 29 kDa, which had a more intense reaction. (2) Common antigenicities between A. cantonensis third stage larvae and snails susceptible to A. cantonensis, were observed in a range of molecular weights of 14.3 to 97.4 kDa, especially A. fulica and B. glabrata, where we detected many bands in molecular weight range of 18.4 to 43 kDa. Based on the common antigenicities between A. cantonensis and snails susceptible to A. cantonensis, it is possible that the common antigenicities are one of the factors defining the different susceptibilities of various species of snails to A. cantonensis, and more bands are seen with increasing infection rates with A. cantonensis. Of those bands, the protein with the molecular weight of 29 kDa may be the main common antigen between the A. cantonensis adult worm, the third stage larvae and the snails susceptible to A. cantonensis.     

Group 2 innate lymphoid cells support hematopoietic recovery under stress conditions

The cell-cycle status of hematopoietic stem and progenitor cells (HSPCs) becomes activated following chemotherapy-induced stress, promoting bone marrow (BM) regeneration; however, the underlying molecular mechanism remains elusive. Here we show that BM-resident group 2 innate lymphoid cells (ILC2s) support the recovery of HSPCs from 5-fluorouracil (5-FU)–induced stress by secreting granulocyte-macrophage colony-stimulating factor (GM-CSF). Mechanistically, IL-33 released from chemo-sensitive B cell progenitors activates MyD88-mediated secretion of GM-CSF in ILC2, suggesting the existence of a B cell–ILC2 axis for maintaining hematopoietic homeostasis. GM-CSF knockout mice treated with 5-FU showed severe loss of myeloid lineage cells, causing lethality, which was rescued by transferring BM ILC2s from wild-type mice. Further, the adoptive transfer of ILC2s to 5-FU–treated mice accelerates hematopoietic recovery, while the reduction of ILC2s results in the opposite effect. Thus, ILC2s may function by “sensing” the damaged BM spaces and subsequently support hematopoietic recovery under stress conditions.     

Critical roles of c-Kit tyrosine residues 567 and 719 in stem cell factor-induced chemotaxis: contribution of src family kinase and PI3-kinase on calcium mobilization and cell migration

Stem cell factor (SCF) has crucial roles in proliferation, survival, and differentiation of hematopoietic stem cells and mast cells through binding to c-Kit receptor (KIT). Chemotaxis is another unique function of SCF. However, little is known about the intracellular signaling pathway of SCF/KIT-mediated cell migration. To investigate the signaling cascade, we made a series of 22 KIT mutants, in which tyrosine (Y) residue was substituted for phenylalanine (F) in the cytoplasmic domain, and introduced into BAF3 cells or 293T cells. On stimulation with SCF, BAF3 expressing KIT(WT)(WT) showed cell migration and Ca(2+) mobilization. Among 22 YF mutants, Y567F, Y569F, and Y719F showed significantly reduced cell migration and Ca(2+) mobilization compared to WT. In Y567F, Lyn activation on SCF stimulation decreased and C-terminal Src kinase (Csk) suppressed KIT-mediated Ca(2+) influx and cell migration, suggesting that Y567-mediated Src family kinase (SFK) activation leads to Ca(2+) influx and migration. Furthermore, we found that p38 mitogen-activated protein kinase (p38 MAPK) and Erk1/2 were also regulated by Y567/SFK and involved in cell migration, and that p38 MAPK induced Ca(2+) influx, thereby leading to Erk1/2 activation. In Y719F, the binding of phosphatidylinositol 3'-kinase (PI3K) to KIT was lost and KIT-mediated cell migration and Ca(2+) mobilization were suppressed by PI3K chemical inhibitors or dominant-negative PI3K, suggesting the involvement of Y719-mediated PI3K pathway in cell migration. Combination of Csk and the PI3K inhibitor synergistically reduced cell migration, suggesting the cooperation of SFK and PI3K. Taken together, these results indicate that 2 major KIT signaling pathways lead to cell migration, one is Y567-SFK-p38 MAPK-Ca(2+) influx-Erk and the other is Y719-PI3K-Ca(2+) influx.